Retrovirus & Opportunistic Infections Part II (cont.)
There were several presentations in a symposium that summarized potential strategies for preventing transmission. Dr. Myron Cohen from the University of North Carolina, Chapel Hill, presented on the potential role antiretroviral therapy may have on preventing HIV transmission. He discussed animal data that has shown the potential efficacy of pre- and post-exposure prophylaxis . He talked about studies that are utilizing pre-exposure prophylaxis, as well as recent CDC guidelines for nonoccupational post exposure prophylaxis. He did emphasize the lack of efficacy data and concerns about toxicity and the possibility of selecting for resistance if transmission were to occur. Data was also presented regarding the relationship between antiretroviral therapy and viral load in blood and genital secretions. This discussion focused on how different drugs achieve different levels in the genital tract and how this might be important with regards to the impact antiretroviral therapy may have on HIV transmission.
In the same session there was a presentation given by Dr. Sharon Hillier from the University of Pittsburgh, School of Medicine, and the Magee Women's Hospital in Pennsylvania. She summarized issues unique to women, one of the fastest growing groups with HIV infection around the world. She talked about some of the cultural and social problems faced by women that limit their ability to protect themselves from HIV infection, as well as the importance of them being empowered by the availability of methods that do not rely on the use of the male condoms. This included discussion of the female condom and diaphragm, as well as the development of various agents that might alter vaginal pH in order to reduce infection, as well as the development of antiviral compounds, or so-called 'microbicides'. In fact, she noted that there has been a tremendous amount of interest and research in microbicides development over the last several years with 5 products in 6 large microbicide trials that are anticipated to report results as soon as 2007 or 2008.
There were several important presentations describing issues related to HIV transmission. Dr. Viani and colleagues studied recently infected adolescents in a multicenter adolescent trial network study called 'ATN 022'. These investigators used the detuned assay to identify adolescents that were recently infection, probably within the last 180 days. These individuals were from 15 different cities and were assessed for the presence of virus with any major drug resistant mutation. They showed that approximately 18 percent had evidence of resistance; the majority being resistant to NNRTIs. This is consistent with what has been seen in adult cohorts of recently infected individuals, and emphasizes the importance of looking for drug resistance prior to initiating antiretroviral therapy.
There were several important presentations at this meeting related to the pharmacokinetic interactions between drugs. One study assessed the interaction between lopinavir/ritonavir and tipranavir, two PIs that are often active in treatment-experienced subjects. They found that by increasing the dose of lopinavir/ritonavir to the equivalent to 4 capsules twice a day with an extra dose of ritonavir, or by giving extra doses of ritonavir with standard doses of lopinavir/ritonavir they were partly able to overcome some of the reduction in lopinavir levels seen when co-administered with tipranavir. Despite this, there was considerable variability in lopinavir levels and the authors recommended that if used together therapeutic drug monitoring should be considered.
Dr. Pham and colleagues at Johns Hopkins looked at the interaction between lopinavir/ritonavir and atazanavir. In this case they found with standard doses reasonably good levels of both drugs were maintained, although the clinical situation which these two drugs might be used in combination remains to be seen. Because there are many people who have extensive drug resistance and are looking at novel agents that they can use together, one study by Dr. Scholler from Tibotec, analyzed the drug-drug interaction between their new NNRTI TMC-125, with a recently approved PI called tipranavir that has been used for treatment-experienced patients. Unfortunately, they found that when these two drugs were used in combination there was a marked reduction in the TMC 125 levels, making this a nonviable option.
Finally, another pharmacokinetic study that may be relevant for the practitioner analyzed data from subjects taking both lopinavir/ritonavir and the lipid-lowering drug rosuvastatin. In this case lopinavir levels were unchanged but there was a 1.5 to 2-fold increase in rosuvastatin levels, the latter being based upon data from historical controls. Based upon these results the authors suggest that these drugs could be used together, although probably best to start with low dose rosuvastatin and titrate up based upon response to therapy.
There were several presentations looking at the potential utility of screening for STIs in asymptomatic individuals. The significance of this is that the presence of STIs is a marker for unsafe sexual activity and if active infection occurs or the STIs are transmitted it can be associated with morbidity as well as increased risk of HIV transmission. One study by Dr. Rieg and colleagues from Harbor-UCLA Medical Center screened 212 HIV-infected men who have sex with men followed in an urban clinic. Survey information was collected along with testing for syphilis as well as gonorrhea and chlamydia in urine as well as at the pharynx and the rectal sites. These investigators found that 13 percent of subjects tested positive for 35 STIs, with many identified at the rectal and pharyngeal mucosa, locations that are not routinely screened in clinical practice. Those with STIs were all treated and proven to be cured of this infection and then all enrolled subjects were tested again at 6 months. At the second visit many subjects from the cohort were found to be newly infected. The strongest predictor of being infected was having had at least two partners in the last six months. This kind of data will be important for ultimately defining the optimal strategies for screening at risk individuals for asymptomatic STIs.
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Last Editorial Review: 2/8/2006